OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group （water）， model group （water）， Shengmai powder low-， medium-， and high-dose groups [2.61， 5.22 and 10.44 g/kg （based on crude drug dosage）] and positive control group （metoprolol， 30 mg/kg）， with 10 mice in each group. Except for the blank group， all other groups were subcutaneously injected with D-galactose， and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling， the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine （TCM） syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action， the percentage of immobility time， and the swimming exhaustion time of mice. The contents of aspartate transaminase （AST）， creatine kinase （CK） and lactate dehydrogenase （LDH） in the serum of mice were detected； cardiac function indexes [heart rate， left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， left ventricular mass index and whole heart mass index] were all detected； the histopathological morphology of mice myocardium was observed； the level of cardiomyocyte apoptosis in mice was detected； mRNA expression levels of B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Cleaved-caspase-3 in myocardial tissue of mice were detected； the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 （RyR2） and phospholamban （PLB）] in myocardial tissue of mice were detected. RESULTS Compared with the blank group， the body weight， total distance of open field action， swimming exhaustion time， LVEF， LVEDD， Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened （P＜0.05）； TCM syndrome score， the percentage of immobility time， heart rate， LVESD， left ventricular mass index， whole heart mass index， cardiomyocyte apoptosis rate， the contents of CK， LDH and AST in serum， mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased （P＜0.05）； there were inflammatory cell infiltration， disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder， most of the above quantitative indexes in mice were significantly reversed （P＜0.05）， the inflammatory cell infiltration in myocardial tissue was reduced， and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function， reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Objective:To evaluate the relationship between the mechanism of propofol inhibiting carotid sinus baroreflex (CSR) and GluR2 subunit-containing AMPA receptors in the nucleus ambiguus of rats with type 2 diabetes mellitus (T2DM).Methods:SPF healthy male Sprague-Dawley rats, aged 3 weeks, were selected and fed a high glucose and high fat diet for 6 weeks, and then streptozotocin 30 mg/kg was intraperitoneally injected to prepare a T2DM model of rats. Twenty-four T2DM rats were divided into 4 groups ( n=6 each) using a random number table method: diabetes mellitus-normal saline group (DN group), diabetes mellitus-propofol group (DP group), AMPA receptor agonist-normal saline group (AN group), and AMPA receptor agonist-propofol group (AP group). Another 12 normal rats were selected and divided into 2 groups ( n=6 each) using a random number table method: normal-normal saline group (NN group) and normal-propofol group (NP group). AMPA receptor agonist mibamitor 1 nmol/L (50 nl) was injected into the nucleus ambiguus using a micropipette at 30 min before perfusion of isolated carotid sinus in AN and AP groups. Propofol 45 mg·kg -11·h -1 was infused for 2 h via the femoral vein in NP group, DP group and AP group, and the equal volume of normal saline was given instead in the other groups. A model for perfusing isolated carotid sinus was developed at 20 min after infusion of propofol or normal saline, the intracarotid sinus pressure (ISP)-mean arterial blood pressure (MAP) curve was drawn, and CSR parameters such as maximum slope (PS), threshold pressure (TP), saturation pressure (SP), equilibrium pressure (EP), maximum decrease in MAP reflexivity (RD), and carotid sinus baroreceptor operating range (OR) were recorded. Brain tissues were taken at the end of perfusion, and the expression of GluR2 subunit in the nucleus ambiguus was detected by Western blot and immunofluorescence. Results:Compared with the corresponding normal saline groups (NN group, DN group, AN group), PS and RD were significantly decreased, TP, SP and OR were increased ( P<0.05), and the ISP-MAP curve was shifted upward in propofol groups (NP group, DP group, AP group), the expression of GluR2 subunit in the nucleus ambiguus was down-regulated in NP and DP groups ( P<0.05), and no significant change was found in the expression of GluR2 subunit in the nucleus ambiguus in AP group ( P>0.05). Compared with NP group, PS and RD were significantly decreased, TP, SP and OR were increased ( P<0.05), the ISP-MAP curve was shifted upward, and the expression of GluR2 subunit in the nucleus ambiguus was down-regulated in DP group ( P<0.05). Compared with DP group, PS and RD were significantly increased, TP, SP and OR were decreased ( P<0.05), the ISP-MAP curve was shifted downward, and the expression of GluR2 subunit in the nucleus ambiguus was up-regulated in AP group ( P<0.05). Conclusions:The mechanism by which propofol inhibits CSR may be related to down-regulation of the expression of GluR2 subunits-containing AMPA receptors in the nucleus ambiguus of rats with T2DM.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective:To evaluate the effect of down-regulating lncRNA LINC00263 targeting miR-4458 on the proliferation, migration, invasion and radiosensitivity of breast cancer SK-BR-3 cells.Methods:The expression differences of LINC00263 in breast cancer tissues, adjacent tissues, normal breast epithelial cells and breast cancer cells were determined by qRT-PCR. Transfection of LINC00263 shRNA in breast cancer SK-BR-3 cells down-regulated the expression of LINC00263, and the cloning experiment was used to detect the radiosensitivity. Breast cancer SK-BR-3 cells were treated with 6 Gy irradiation. CCK-8 assay was employed to detect cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Transwell chamber test was performed to detect cell migration and invasion. Western blot was used to detect the expression levels of C-Caspase-3 and C-Caspase-9, MMP-2 and MMP-9 proteins. Bioinformatics software predicted that LINC00263 and miR-4458 had complementary binding sites, and the luciferase reporter system was utilized determine the targeting relationship between LINC00263 and miR-4458. LINC00263 shRNA and miR-4458 inhibitor were co-transfected into breast cancer SK-BR-3 cells, and 6 Gy irradiation was given to detect the changes in cell proliferation, apoptosis, invasion and migration.Results:The expression level of LINC00263 in breast cancer tissues was higher than that in adjacent tissues. The expression level of LINC00263 in breast cancer cells was higher compared with that in normal breast epithelial cells. The radiosensitivity of breast cancer SK-BR-3 cells was increased after transfection of LINC00263 shRNA. Transfection of LINC00263 shRNA and radiation exerted a synergistic effect, jointly inhibited breast cancer cell proliferation, migration and invasion, promoted cell apoptosis, up-regulated the expression levels of C-Caspase-3 and C-Caspase-9 proteins in cells, and down-regulated those of MMP-2 and MMP-9 proteins. Down-regulation of LINC00263 targetedly up-regulated miR-4458 expression. miR-4458 inhibitor reversed the inhibitory effect of LINC00263 shRNA combined with radiation on the proliferation, migration, invasion and apoptosis promotion of breast cancer SK-BR-3 cells.Conclusion:Down-regulating lncRNA LINC00263 targeting miR-4458 inhibits the proliferation, migration and invasion of breast cancer SK-BR-3 cells, and improves cell radiosensitivity.

ObjectiveTo investigate the clinical features of drug-induced liver injury (DILI) caused by antitumor drugs during the treatment of malignant tumors. MethodsA retrospective analysis was performed for the clinical data of 56 patients who were diagnosed with malignant tumors in Henan Provincial People′s Hospital from January 2015 to December 2016 and experienced DILI during the treatment with antitumor drugs, including sex, age, type of primary tumor, hepatotropic virus infection, liver function, type of chemotherapeutics, onset time of liver injury, application of liver-protecting drugs, and outcome of liver injury. ResultsAmong the 56 patients with DILI caused by antitumor drugs, 30 (53.6%) had hepatocellular injury, and 45 (80.4%) had mild liver injury. FOLFOX, GP/DP, and CHOP were the most common regimens for DILI, and of all 56 patients, 50 (89.3%) had DILI caused by multiple drugs. Platinum-based drugs, anti-microtubule agents, and alkylating agents were the common drugs causing DILI. Of all 56 patients, 35 (62.5%) developed DILI within 1-2 weeks after medication. ConclusionDILI caused by antitumor drugs mainly has a mild degree and hepatocellular injury type is the most common clinical type. Platinum-based antitumor drugs and related chemotherapeutic regimens are the most common drugs for DILI. A combination of multiple antitumor drugs is more likely to cause DILI, and patients with such DILI often have a good prognosis.

Objective To evaluate the clinical value of CTPA combined with V/Q imaging to guide the end point of anticoagulant therapy in reducing the recurrence rate of pulmonary embolism. Methods A total of 159 cases of pulmonary embolism diagnosed by CTPA were randomly divided into experimental group(n=80)and control group(n = 79). After the regular low molecular weight heparin and warfarin anticoagulation therapy ,the experimental group used the CTPA combined with V/Q imaging to evaluate the pulmonary embolism absorption ,to guide the end point of anticoagulant therapy and to evaluate the recurrence rate of pulmonary embolism at the end of 1-year treatment. But in control group ,only CTPA was used to guide the treatment and then the recurrence rate in 2 groups was compared. Results The anticoagulant treatment course of experimental group was(5.90 ± 1.80) months,which was significantly longer than that of control group(3.57 ± 1.09)months(P<0.05). The recurrence rate of experimental group was significantly lower than that of control group(7.5%vs. 22.8%)after 1-year treatment (P<0.05). However,there was no significant difference between 2 groups(8.75%vs 3.80%)in the rate of bleed-ing during anticoagulation therapy (p>0.05).Conclusions CTPA combined with V/Q imaging to guide the end point of anticoagulant therapy for pulmonary embolismhas important clinical value in reducing the recurrence rate of pulmonary embolism.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers in China, but the underlying molecular mechanism of ESCC is still unclear. Involvement of micro-RNAs has been demonstrated in cancer initiation and progression. Despite the reported function of miR-503 in several human cancers, its detailed anti-oncogenic role and clinical significance in ESCC remain undefined. In this study, we examined miR-503 expression by qPCR and found the downregulation of miR-503 expression in ESCC tissue relative to adjacent normal tissues. Fur-ther investigation in the effect of miR-503 on ESCC cell proliferation, migration, and invasion showed that enhanced expression of miR-503 inhibited ESCC aggressive phenotype and overexpres-sion of CCND1 reversed the effect of miR-503-mediated ESCC cell aggressive phenotype. Our study further identified CCND1 as the target gene of miR-503. Thus, miR-503 functions as a tumor suppressor and has an important role in ESCC by targeting CCND1.

Objective To study the clinical features, effects of therapeutic regimen and prognosis of patents with mantle cell lymphoma (MCL). Methods Clinical data of 27 MCL patients admitted in Tianjin Medical University Cancer Institute&Hospital from January 2008 to December 2014 were retrospectively analyzed. Cox regression analysis was used to analyze influencing factors of prognosis of MCL. Results The median age was 68 years old for 27 patients, and the male-to-female ratio was 4.4∶1. Ann Arbor staging showed that 25 cases were stageⅢ-Ⅳ(92.6%), 8 cases were heptosplenomegaly (29.6%), 7 cases showed extranodal involvement (25.9%). ECOG scoring showed that 4 cases with scores of 2-4 (14.8%), 8 cases were 0-3 (29.6%), 14 cases were 4-5 (51.9%) and 5 cases were 6-11 (18.5%). The Ki-67 index≤30%was found in 9 cases (33.3%), and>30%was found in 18 cases (67.7%). Patients with B symptom was found in 10 (37.0%). The elevated lactate dehydrogenase (LDH) was found in 17 cases (63.0%). The increased Beta 2- microglobulin was found in 8 cases (29.6%). Seven patients were found with bone marrow involvement. The total effective rate (ORR) was 81.8%in group with R-CHOP method, and the ORR was 68.8%in group with CHOP method. Multivariate analysis showed that age, LDH and Ki-67 were independent factors influencing the prognosis of MCL (P<0.05). Conclusion Most patients with MCL are found in advanced stage. Patients with age>60 years, elevated LDH and Ki-67 index>30%are with poor prognosis.

ObjectiveTo investigate the relationship between syndrome differentiation types and the objective indexes of fatty liver.MethodsA cross-sectional study was adopted. Clinical observation table of fatty liver for TCM diagnostic performance was used to collect the data of patients and cluster analysis was adopted for syndrome differentiation. The difference of the objective indexes among different syndromes was studied.ResultsFatty liver showed more severity in spleen Qi deficiency and dampness group compared with heart and liver yin deficiency group(χ2=8.218,P=0.041). Patients in the spleen and stomach Qi deficiency group had less smoking history(χ2=8.416,P=0.038). Patients in the spleen Qi deficiency and dampness group had higher AST, TP, ALP and WHR indexes and lower Alb.ConclusionsDifferences of objective indexes in different fatty liver syndromes can be used for enriching syndrome differentiation contents, and provide the basis for microcosmic syndrome differentiation of fatty liver.